Comparative single-cell analyses reveal evolutionary repurposing of a conserved gene programme in bat wing development

Bats are the only mammals capable of self-powered flight, an evolutionary innovation based on the transformation of forelimbs into wings. The bat wing is characterized by an extreme elongation of the second to fifth digits with a wing membrane called the chiropatagium connecting them. Here we investigated the developmental and cellular origin of this structure by comparing bat and mouse limbs using omics tools and single-cell analyses. Despite the substantial morphological differences between the species, we observed an overall conservation of cell populations and gene expression patterns including interdigital apoptosis. Single-cell analyses of micro-dissected embryonic chiropatagium identified a specific fibroblast population, independent of apoptosis-associated interdigital cells, as the origin of this tissue. These distal cells express a conserved gene programme including the transcription factors MEIS2 and TBX3, which are commonly known to specify and pattern the early proximal limb. Transgenic ectopic expression of MEIS2 and TBX3 in mouse distal limb cells resulted in the activation of genes expressed during wing development and phenotypic changes related to wing morphology, such as the fusion of digits. Our results elucidate fundamental molecular mechanisms of bat wing development and illustrate how drastic morphological changes can be achieved through repurposing of existing developmental programmes during evolution.

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Journal
Nature Ecology & Evolution
Published
2025-07-16
DOI
https://doi.org/10.1038/s41559-025-02780-x
Citations
6
Primary Topic
Bat Biology and Ecology Studies
Type
article
Field-Weighted Citation Impact
18.16
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article

Comparative single-cell analyses reveal evolutionary repurposing of a conserved gene programme in bat wing development

Stefan A. Haas, Tobias Zehnder, Nicolas J. Fasel, Martin Vingron et al.
6 citations
Nature Ecology & Evolution
Bat Biology and Ecology Studies
18.16
article

Comparative single-cell analyses reveal evolutionary repurposing of a conserved gene programme in bat wing development

Stefan A. Haas, Tobias Zehnder, Nicolas J. Fasel, Martin Vingron, Stefan Mundlos, Francisca M. Real, Ariadna E. Morales, René Hägerling, A. Neil Barclay, Darío G. Lupiáñez, Juliane Glaser, Michael Hiller, Bjørt K. Kragesteen, Christian Feregrino, Guillaume Andrey, Magdalena Schindler, Alessa R. Ringel, Anna A. Monaco, Bai-Wei Lo, Marc A. Martı́-Renom, Rose Yinghan Behncke, Igor Ulitsky, Julio C. Hechavarría, Silvia Aldrovandi
article en
6 citations

Abstract

Bats are the only mammals capable of self-powered flight, an evolutionary innovation based on the transformation of forelimbs into wings. The bat wing is characterized by an extreme elongation of the second to fifth digits with a wing membrane called the chiropatagium connecting them. Here we investigated the developmental and cellular origin of this structure by comparing bat and mouse limbs using omics tools and single-cell analyses. Despite the substantial morphological differences between the species, we observed an overall conservation of cell populations and gene expression patterns including interdigital apoptosis. Single-cell analyses of micro-dissected embryonic chiropatagium identified a specific fibroblast population, independent of apoptosis-associated interdigital cells, as the origin of this tissue. These distal cells express a conserved gene programme including the transcription factors MEIS2 and TBX3, which are commonly known to specify and pattern the early proximal limb. Transgenic ectopic expression of MEIS2 and TBX3 in mouse distal limb cells resulted in the activation of genes expressed during wing development and phenotypic changes related to wing morphology, such as the fusion of digits. Our results elucidate fundamental molecular mechanisms of bat wing development and illustrate how drastic morphological changes can be achieved through repurposing of existing developmental programmes during evolution.

Nature Ecology & EvolutionVol. 9(9)
Goethe University Frankfurt (DE), University of Geneva (CH), Institució Catalana de Recerca i Estudis Avançats (ES), Centre National de la Recherche Scientifique (FR), Universitat Pompeu Fabra (ES), Université de Montpellier (FR), Max Delbrück Center (DE), Senckenberg Research Institute and Natural History Museum Frankfurt/M (DE), Karolinska Institutet (SE), Institut des Sciences de l'Evolution de Montpellier (FR), Centro Andaluz de Biología del Desarrollo (ES), LOEWE Centre for Translational Biodiversity Genomics (DE), Centre for Genomic Regulation (ES), Berlin Institute of Health at Charité - Universitätsmedizin Berlin (DE), Centro Nacional de Análisis Genómico (ES), Max Planck Institute for Molecular Genetics (DE), Institut de Recherche pour le Développement (FR), Weizmann Institute of Science (IL), Charité - Universitätsmedizin Berlin (DE), University of Lausanne (CH)
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Bat Biology and Ecology Studies
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